Mentions:
We previously reported that inhibition of cAMP-dependent PKA activity abolishes rebound stimulation of ICa,L elicited by ACh withdrawal (Wang and Lipsius, 1995). To determine whether exogenous NO stimulates ICa,L via cAMP, SP/NO was tested in the absence and presence of H-89, an inhibitor of cAMP-dependent PKA activity (Chijiwa et al., 1990). As shown in the bar graph in Fig. 11, 100 μM SP/NO elicited a mean increase in ICa,L of 108 ± 35%. In the presence of 5 μM H-89, the stimulatory effect of SP/NO on ICa,L (36 ± 7%) was significantly reduced compared with control (P < 0.05; n = 5). In three additional cells, the concentration of SP/NO was lowered (30 μM) to a level that elicited an increase in ICa,L comparable to that achieved by ACh withdrawal. In the absence and presence of H-89, 30 μM SP/NO elicited a mean increase in ICa,L of 61 ± 5% and 14 ± 5%, respectively (P < 0.001). These findings indicate that NO stimulates ICa,L primarily by increasing cAMP and are consistent with the role of NO signaling in stimulation of ICa,L elicited by ACh withdrawal.

Mentions:
We previously reported that inhibition of cAMP-dependent PKA activity abolishes rebound stimulation of ICa,L elicited by ACh withdrawal (Wang and Lipsius, 1995). To determine whether exogenous NO stimulates ICa,L via cAMP, SP/NO was tested in the absence and presence of H-89, an inhibitor of cAMP-dependent PKA activity (Chijiwa et al., 1990). As shown in the bar graph in Fig. 11, 100 μM SP/NO elicited a mean increase in ICa,L of 108 ± 35%. In the presence of 5 μM H-89, the stimulatory effect of SP/NO on ICa,L (36 ± 7%) was significantly reduced compared with control (P < 0.05; n = 5). In three additional cells, the concentration of SP/NO was lowered (30 μM) to a level that elicited an increase in ICa,L comparable to that achieved by ACh withdrawal. In the absence and presence of H-89, 30 μM SP/NO elicited a mean increase in ICa,L of 61 ± 5% and 14 ± 5%, respectively (P < 0.001). These findings indicate that NO stimulates ICa,L primarily by increasing cAMP and are consistent with the role of NO signaling in stimulation of ICa,L elicited by ACh withdrawal.